DESCRIPTION (Applicant's Abstract): Cocaine dependence and opiate+cocaine dependence are important public health problems. They have proven difficult to treat. New medications must be examined, though behavioral-environmental factors can be expected to act jointly with medication, influencing outcome. Drugs that act at dopamine pathways directly or indirectly alter cocaine intake and other measures in pre-clinical and human studies. One such medication, ritanserin, may be effective for cocaine dependence.Methadone is an effective, well understood medication for treatment of opiate dependence. Methadone+ritanserin may be particularly effective in treating concurrent opiate cocaine dependence. Medication effects can be modulated by setting factors. Visit frequency is a condition we have demonstrated acts jointly with medication. Behavioral therapy enhanced with contingency management procedures also may interact with medication. These studies, like our earlier work, will examine the joint action of medications and treatments elements using logical combinations of interventions. We propose two sets of parallel studies. The baseline behavioral- psychological intervention will be a highly structured professionally delivered therapy (2/wk). In Studies 1 and 2, the cocaine treatment medication will be ritanserin (placebo, 5, or 10 mg). In Studies 3 and 4, ritanserin (0, 5, or 10 mg) + methadone (at 1.1 mg/kg) will be administered to cocaine + opiate dependent patients. Ritanserin components will be double- blind placebo-controlled. There will be 150 patients in each study randomly assigned. Cocaine dependence studies (1 and 2) will be 12 weeks and opiate+cocaine dependence studies (3 and 4) will be 26 weeks. All studies include self-report, standard medical examination with HIV and TB tests, and psychiatric evaluations. Phases are: consent, intake, 2 week stabilization, treatment, and study end periods, with a 3 month follow-up. Major independent variables are medication and dose with setting/treatment variables of visit frequency (2 or 5/week), or standard behavioral vs reinforcer enhanced therapy. In the enhanced therapy, patients will have the opportunity to obtain supplementary reinforcers contingent on drug screen results over successive weeks. Major dependent variables are drug use (2/wk urine screens) and retention, with other secondary analyses. The proposed studies will be carefully conducted clinical trials examining new medications and factors modulating medication effects and treatment outcome. They are logical extensions of our ongoing work and complement our other studies.